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Biomedical subjects

D Winter

Publications and source records attributed to D Winter.

At least 19 recordsLinked to original sources
PubMed1997

Lead-catalysed specific cleavage of ribosomal RNAs.

Ribosomes have long been known to require divalent metal ions for their functional integrity. Pb2+-induced cleavage of the sugar-phosphate backbone has now been used to probe for metal binding sites in rRNA. Only three prominent Pb2+cleavages have been detected, with cleavage sites 5' of G240 in 16S rRNA and two sites 5' of A505 and C2347 in 23S rRNA. All cleavages occur in non-paired regions of the secondary structure models of the rRNAs and can be competed for by high concentrations of Mg2+, Mn2+, Ca2+ and Zn2+ ions, suggesting that lead is bound to general metal binding sites. Although Pb2+ cleavage is very efficient, ribosomes with fragmented RNAs are still functional in binding tRNA and in peptidyl transferase activity, indicating that the scissions do not significantly alter ribosomal structure. One of the lead cleavage sites (C2347 in 23S RNA) occurs in the vicinity of a region which is implicated in tRNA binding and peptidyl transferase activity. These results are discussed in the light of a recent model which proposes that peptide bond formation might be a metal-catalysed process.

Anti-Bacterial Agents↗
PubMed1995

Transient dominance of the early primary immune response by a highly conserved B-cell clone that is distinguished by its lack of memory, high threshold of activation, and a high affinity.

We establish here that the very early primary response to the hapten phthalate (Xmp) is distinguished by a restricted heterogeneity with over 80% of the anti-Xmp antibodies expressing a single well-defined cross-reactive idiotype (CRIXmp-1) associated with a previously described highly conserved clonotype that is expressed by most inbred strains of mice and many outbred mouse populations as well. The characteristic early dominance of this one clonotype in the primary response is transient. While the CRIXmp-1 clonotype is present later in the primary and throughout the secondary response, it represents only a very small proportion of the total anti-Xmp antibody population at these times. The early dominance of the single clonotype is rapidly replaced by a heterogeneous population of antibodies. Differential activation thresholds for the primary response clonotype (CRIXmp-1) and secondary response clonotypes, and the failure of the dominant primary response clonotype to expand in the secondary response (i.e., absence of memory) suggest the presence of two distinct B-cell lineages.

Animals↗
PubMed1993

The importance of the role of the patient in the outcome of schizophrenia.

The Family Interpersonal Perception Test (FIPT) was used to explore the relationships between schizophrenic patients and their parents, and how these related both to relapse in the year after discharge and to improvement in social functioning. Forty schizophrenic patients and their parents were tested during their first ever admission to hospital and again two years later. Parents' and patient's views of each other were more negative in those with worse outcome, but what most significantly distinguished groups with different outcomes was how patients expected their parents to see them. The FIPT, therefore, reveals patterns of interaction in which the patient's role in outcome is at least as important as that of the parents, and can aid the identification of specific features with which to work in therapy.

Adolescent↗
PubMed1992

Nucleotide sequence of messenger RNA encoding VHDJH and VKJK of a highly conserved idiotype-defined primary response anti-hapten antibody.

The primary humoral immune response of mice to the hapten phthalate (Xmp) is focused upon two adjacent immunodominant negatively charged carboxyl groups on a benzene ring that are in positions meta and para to the azolinkage (i.e., Xmp) to the protein carrier keyhole limpet hemocyanin. A significant fraction of the anti-Xmp antibodies raised in several different inbred mouse strains (BALB/c, DBA/2, A/HeHa; C3H, and SM/J), and many wild mouse populations express a cross-reactive Id, CRIXmp-1. This CRIXmp-1 is conspicuously absent in C57BL/6 mice. In order to obtain a better understanding of the events and parameters that influence the selection and regulation of the primary response B cell repertoire, and to explore the structural basis of Ag binding, we have determined the nucleotide sequence of the entire V region gene complexes, which encode the H and L chains of these highly conserved and dominant CRIXmp-1+ antibodies. Our data establish that the H chain gene complex consists of a single VH germ-line gene that is identical to VH Oxazolone-1, encoding the H chain of another highly conserved and dominant cross-reactive Id family associated with the primary response to Oxazolone. In CRIXmp-1+ Xmp-specific hybridomas this gene is joined to a limited set of D region sequences that express a conserved amino acid motif-GLR. At least three of the five D regions examined are coded for by DFL16.2. This VHD complex can be utilized with one of three different JH region genes (JH1, JH2, and JH4) without any significant effect upon antibody fine specificity or Id. In spite of this lack of JH fidelity all of the CRIXmp-1+ hybridomas have precisely maintained the same length in the H chain CDR3 and FRW4 by altering either the length of the D segment or the length of JH. Nucleotide sequence analysis of the VL gene complex of CRIXmp-1+ anti-Xmp antibodies indicates that the L chain V region is also encoded by a single germ-line gene. The amino acid sequence predicted from the nucleotide sequence of the VKJK from Xmp-specific CRIXmp-1+ hybridomas is identical to the sequence of the anti-arsonate antibody 1210.7, which is the prototype of another Id family (CRI) that is conserved and dominant in BALB/c mice.

Acute-Phase Reaction↗
PubMed1990

Umbilical and uterine artery flow velocity waveforms in normal pregnancy and pregnancy induced hypertension.

Umbilical and uterine artery Doppler studies were carried out in 113 cases of normal pregnancy and in 32 patients with pregnancy induced hypertension (PIH). The results were analyzed by calculating the systolic/diastolic (S/D) ratio. In normal pregnancy the umbilical velocity wave S/D ratio declined from 3.9 to 2.1 from 20th week to term, and the uterine wave S/D ratio remained constant between 1.8 and 1.9. In many cases of severe PIH the umbilical and uterine artery velocity wave S/D ratios were raised, indicating increased resistance to the blood flow. The changes of umbilical waveforms appeared earlier than those of the uterine arterial waveforms.

Adult↗
PubMed1989

Pregnancy surveillance with Doppler velocimetry of uterine and umbilical arteries.

Previous studies with Doppler velocimetry have demonstrated a strong correlation between abnormal waveforms and fetal-maternal disease. This study was designed to evaluate the potential role of Doppler velocimetry as a screening test in routine prenatal care. Two hundred fifty-five pregnant women had routine monthly Doppler (systolic/end-diastolic ratio) studies on the uterine and umbilical arteries starting in the twentieth week of gestation. When a cutoff value of 3 was used at 30 weeks for the umbilical arteries, there were 35 (13%) positive tests. In 20 of these values fell to less than 3 in the ensuing weeks and were considered false positive. The remaining 15 babies demonstrated positive clinical pathologic correlates. When a value of 2.6 was used at 26 weeks for uterine arteries, there were nine positive results, seven of which had clinical pathologic correlates. This study suggested an overall positivity rate of 7%; therefore it provides encouragement for a larger venture in which screening and impact on decision making are evaluated.

Adult↗
PubMed1988

Prenatal surveillance using nonstress testing and Doppler velocimetry.

One hundred forty pregnant women referred to our prenatal testing laboratory for conventional nonstress testing (NST) also had a Doppler study of the umbilical arteries. The outcomes of 88 women with abnormal testing (NST or Doppler) were compared with the outcomes of 52 women who had normal results on both tests. The results demonstrated that 50% of the fetuses with decreased flow velocity who later developed an abnormal NST were growth-retarded, 75% required a cesarean section, and 63% were admitted to the neonatal intensive care unit. Development of an abnormal NST in the presence of normal velocimetry studies occurred most frequently in the postdates pregnancy; 32% required cesarean section for fetal distress. Knowledge of the umbilical circulation through Doppler studies may be of benefit when selecting patients for NST and when interpreting results.

Blood Flow Velocity↗
PubMed1988

Uterine and umbilical artery Doppler velocimetry in postterm pregnancy.

Uterine and umbilical artery Doppler velocimetry was carried out on 149 women whose pregnancies went to 41 weeks or beyond. Flow velocity was not altered even in the presence of other signs suggestive of fetal compromise. It appears that the postdate syndrome is not associated with significant alterations in the maternal or umbilical blood flow prior to the onset of labor.

Arteries↗
PubMed1987

NAPROS: a semiautomatic user-friendly anaesthetic record system.

NAPROS is a semiautomatic, inexpensive, and easy-to-use anaesthetic record system. It is based on an ACORN (BBC-Model B) microcomputer that is linked to a non-invasive arterial pressure monitor (DIN-AMAP 845a) and an inhalation anaesthetic monitor (Engstroem EMMA) for automatic collection of measured data. The following functions have been implemented: Automatic registration of cardiovascular data and concentration of anaesthetic inhalation agents. Graphical or numerical representation of fluid-balances. Possibility to recall dosage information for drugs and drops. Printing of a final anaesthetic report at the end of anaesthesia. Definite advantages of NAPROS are: The number of hours saved by the computer record over manual data entry is 8 hours. - Better acceptance by users.

Anesthesiology↗
PubMed1987

The significance of absent end-diastolic velocity in umbilical artery velocity waveforms.

Doppler umbilical artery velocimetry has been used to study high-risk pregnancies. The most extreme waveform abnormality is the absence of end-diastolic velocity. To examine the significance of this finding, events outcome was evaluated in 161 women studied between 31 and 36 weeks. Ten had absence of end-diastolic velocity. When compared with fetuses with normal and less severely abnormal waveforms, there was a higher incidence of intrauterine growth retardation, pregnancy-induced hypertension, cesarean section for fetal distress, neonatal intensive care unit admission, and low Apgar scores. Average birth weight and gestational age at delivery were lower. Five other fetuses with absence of end-diastolic velocity were identified that were delivered between 27 and 30 weeks, making a total of 15 patients with absence of end-diastolic velocity. Of 12 patients monitored, 11 had an abnormal fetal heart rate pattern. Four fetuses had lethal anomalies. There were eight perinatal deaths. Acute or chronic hypoxia was evident in all fetuses with absence of end-diastolic velocity. Absent end-diastolic velocity represents a unique and severe fetal condition that cannot be identified by present surveillance methods and requires a Doppler study for diagnosis.

Blood Flow Velocity↗
PubMed1987

The clinical significance of Doppler umbilical artery velocimetry in the small for gestational age fetus.

Fifty-four women who were delivered of small for gestational age infants were studied antenatally by serially continuous-wave Doppler velocimetry. Outcomes were compared in the normal and abnormal systolic/diastolic ratio groups. Seventy-eight percent had an abnormal systolic/diastolic ratio. The group with an elevated systolic/diastolic ratio had a significantly higher incidence of abnormal fetal heart rate, pregnancy-induced hypertension, oligohydramnios, cesarean section for fetal distress, and admission into the neonatal intensive care unit. One third of the newborns required intermittent positive pressure ventilation. Average birth weight and gestational age at delivery were significantly lower and there were six perinatal deaths in the group with an elevated systolic/diastolic ratio and none in the group with a normal systolic/diastolic ratio. These data suggest that the small for gestational age fetus with normal umbilical artery velocimetry is at significantly lower risk than are those with abnormal ratios. This implies that management of the small for gestational age fetus may now be aided by a functional classification based on the umbilical artery velocity waveform.

Blood Flow Velocity↗
PubMed1987

A classification of hypertension in pregnancy based on Doppler velocimetry.

We studied 136 pregnant women with hypertension with Doppler velocimetry of the uterine and umbilical arteries. The patients were classified into four groups according to the values of the systolic/diastolic ratios. The first group had normal ratios in both the umbilical and uterine arteries. The second group had elevated umbilical ratios and normal ratios in the uterine arteries. The third group had elevated uterine artery systolic/diastolic ratios with normal umbilical artery values, and the fourth group had elevated systolic/diastolic ratios in both vessels. Women in the group with normal ratios in both the umbilical and uterine arteries were delivered of infants with a birth weight (mean +/- SD) of 3261 +/- 522 gm and gestational age of 39 +/- 2 weeks. The values for the three groups with abnormal velocimetry were: those with elevated umbilical ratios and normal ratios in the uterine arteries: body weight = 2098 +/- 811 gm, gestational age = 35.7 +/- 3.2 weeks; those with elevated uterine artery ratios with normal umbilical artery values: 2464 +/- 722 gm, gestational age = 36.3 +/- 3 weeks; and those with elevated systolic/diastolic ratios in both vessels: body weight = 1627 +/- 697 gm, gestational age = 33.3 +/- 2.7 weeks (p less than 0.01; p less than 0.001). There were 27 small for gestational age infants delivered during this study. Doppler velocimetry studies were abnormal in 26 of them (96%). Results show that Doppler-derived vascular patterns correlate well with normal and adverse perinatal outcome. A description of the uterine and umbilical systolic/diastolic ratios should be part of the clinical evaluation of all pregnant women with hypertension. This should lead to better treatment protocols and improved clinical outcome.

Adult↗
PubMed1987

Uterine artery Doppler velocimetry: the significance of divergent systolic/diastolic ratios.

Continuous wave Doppler studies were carried out on both uterine arteries in 71 pregnant women from the twentieth week of gestation onward. Analysis of the waveform included the systolic/diastolic ratio and the presence or absence of a diastolic notch. In the current study, these ratios from 31 women with left/right systolic/diastolic difference, (between left and right uterine arteries) were compared with those of women having normal ratios. A normal left/right systolic/diastolic ratio difference of 0.3 with SD of 0.3 was found. When the left/right difference was plotted against the left/right averaged systolic/diastolic ratio, a correlation coefficient of 0.7 was noted (p less than 0.001). Significant outcome differences were noted between normal and abnormal left/right difference systolic/diastolic ratios in the perinatal parameters of gestational age at delivery, fetal weight, pregnancy-induced hypertension, proteinuria, and intrauterine growth retardation. Divergent uterine artery ratio findings are a result of one artery being the dominant supplier to the placenta. The majority of women with an elevated systolic/diastolic ratio seem to have divergent uterine blood supply to the uterus and placenta. These data suggest that errors in placentation site contribute to the development of preeclampsia and growth retardation in the fetus.

Arteries↗
PubMed1987

Diagnostic utility of hepatobiliary scintigraphy with 99mTc-DISIDA in neonatal cholestasis.

We retrospectively evaluated the utility of hepatobiliary scintigraphy and various clinical factors in differentiating intrahepatic cholestasis from biliary atresia in 28 consecutive infants with neonatal cholestasis. One millicurie of technetium-labeled diisopropyliminodiacetic acid (DISIDA) was administered intravenously, and images were obtained for up to 24 hours or until gastrointestinal excretion was noted. Nine separate studies in seven infants with biliary atresia were correctly interpreted as showing no gastrointestinal excretion of radionuclide. Of the 21 patients with intrahepatic cholestasis, only nine had gastrointestinal excretion on the first study; in eight without excretion, a second study was done, and five of these showed gut excretion. All infants with either neonatal hepatitis (six) or inspissated bile syndrome (three) had demonstrable gastrointestinal excretion either on the first or second DISIDA study. However, five of six infants with paucity of intrahepatic bile ducts, two of six infants with cholestasis secondary to total parenteral nutrition, and one infant with cholangiolitis did not show evidence of gastrointestinal excretion. The mean birth weight, mean gestational age, and mean weight at study were significantly greater (P less than 0.005) for infants with biliary atresia without excretion than for infants with intrahepatic cholestasis without excretion. The mean direct bilirubin concentration was 6.0 mg/dL for both infants with biliary atresia and infants with intrahepatic cholestasis without excretion; however, infants with excretion had a significantly lower (P less than 0.02) mean direct bilirubin value of 3.4 mg/dL. Excretion was noted in four infants with total bilirubin values greater than 10.0 mg/dL. The absence of gut excretion on the first DISIDA study was 100% sensitive but only 43% specific for biliary atresia. In infants without gut excretion of DISIDA, birth weight greater than 2200 g was 100% sensitive and 92% specific for biliary atresia. We conclude that DISIDA scanning, together with clinical data, is useful in differentiating extrahepatic from intrahepatic cholestasis. The absence of gut excretion on the first DISIDA study does not necessarily indicate extrahepatic obstruction; the study should be repeated if the diagnosis is not clear.

Bile Ducts, Intrahepatic↗
PubMed1987

Construction and constriction in agoraphobia.

A formulation of agoraphobia is presented in personal construct theory terms. It is hypothesized that the construing of agoraphobics and their spouses is characterized by low cognitive awareness of constructs concerning interpersonal conflict and lack of tenderness; by dilemmas in which the ability to go out implies possible infidelity; and by low self-esteem in the agoraphobic and high self-esteem in their spouse. Evidence in support of these hypotheses is provided by a repertory grid study comparing agoraphobics, non-agoraphobic neurotics, spouses of both client groups, and normal subjects. Features of construing of agoraphobic and spouse are shown to be predictive of the agoraphobic's response to behaviour therapy, and therapeutic improvement to be associated with some reconstruction in the above areas. The role of mutual validation of constructions between agoraphobic and spouse in the maintenance of agoraphobic behaviour is discussed, as are implications for the treatment of agoraphobia.

Adult↗
PubMed1986

Renal failure does not impair the metabolism of morphine.

The pharmacokinetics of morphine were measured using gas chromatography-mass spectrometry (GCMS) with specific ion monitoring after the intramuscular administration of papaveretum to four patients with renal failure (one anephric) and three normals. The apparent t1/2 of absorption and t1/2 of elimination were significantly shorter in the patients with renal failure (P less than 0.05). Morphine glucuronides are eliminated slowly in these patients as expected. Renal failure does not impair the elimination of morphine.

Adult↗